TOXICITY FOR

FERROUS SULPHATE
PARACETAMOL
PACLITAXEL

EDITED
BY MR MOMPATI LETSWELETSE
(CPhT) SECOND YEAR STUDENT

PARACETAMOL:Mechanism of toxicity

Paracetamol is metabolized to N-acetyl-p-benzoquinone

imine (NAPQI).NAPQI is extremely toxic to the liver, as a
result of covalent binding to proteins and nucleic acids.
However, NAPQI is rapidly detoxified by interaction with
glutathione . Overdoses of acetaminophen deplete hepatic
glutathione stores and allow liver injury to occur.
Signs and symptoms
PHASE ONE(<24hrs):nausea,vomiting,pallor,sweating
PHASE TWO(24-72hrs):signs of increasing liver damage(one
may experience upper-quadrant pain)In some cases, acute
kidney failure maybe the clinical manifestation.
PHASE THREE(3-5days):complications of massive hepatic
necrosis leading to hepatic failure with
complications,coagulation defects,hypoglycemia,kidney
failure,cerebral edema,sepsi,multiple organ failure and
death

SIGNS AND SYMPTOMS

Anorexia(lack or loss of appetite for
food)
nausea, or vomiting
hepatic necrosis becomes evident
Acute renal failure

DIAGONOSIS
Liver function tests:Liver function
tests can show if your liver is working
properly.
Prothrombin time (PT) and INR
rates:These tests measure how long it
takes for your blood to clot.
Other useful laboratory studies
include electrolytes, glucose, BUN,
creatinine, liver transaminases, and
prothrombin time

ANTIDOTE:
ACETYLCYSTEINE
Acetylcysteine works to reduce
paracetamol toxicity by replenishing
body stores of the
antioxidant glutathione. Glutathione
react with the toxic NAPQI metabolite
so that it does not damage cells and
can be safely excreted.

SAFETY PROFILE
Safe and can be used in pregnancy..it
causes no harm to the baby,
Contra indicated in allergic patients ,
asthma and post surgery patients.

FERROUS SULPHATE:MECHANISM
OF TOXICITY

Local

Direct corrosive effect on the gastrointestinal(GI)

mucosa manifests with symptoms ranging from
vomiting and diarrhea to haematemesis ( the vomiting of
blood).and melaena(the production of dark sticky faeces containing partly
digested blood, as a result of internal bleeding).Large GI fluid losses may
contribute significant hypovolaemia. Systemic
toxicity does not occur in the absence of GI
symptoms
When the absorbed iron is not bound to protein, it
produces a variety of harmful free radicals. Acute iron
toxicosi causes both a direct corrosive effect on the
gastrointestinal tract and cellular damage due to
circulating unbound iron.

SIGNS AND SYMPTOMS

Low blood pressure

Fast and weak pulse
Hepatorenal failure
Coma
Hypoglycaemia (deficiency of glucose in the bloodstream.)

Metabolic acidosis due to disruption of cellular

metabolism
Acute hepatic failure with jaundice

DIAGONOSIS
Elevation of the white blood count
(> 15,000) or blood glucose (> 150
mg/dL) or visible radiopaque pills on
abdominal
x-ray also suggests significant
ingestion

ANTIDOTE: DESFERRIOXAMINE
Desferrioxamineis a chelating
agent it binds with free iron in the
bloodstream and forms a water
soluble desferroxamine-iron complex.

Safety Profile
Desferrioxamine -iron
complex is renally excreted. If
oliguria(the production of
abnormally small amounts of
urine) or anuria
develop,peritoneal dialysis
or haemodialysismay
become necessary to remove

PACLITAXEL :MECHANISM OF
TOXICITY
Paclitaxel may induce bradyarrhythmia(is a
slow heart rate) and conduction defects
directly through action on the purkinje
system or indirectly through its vehicle,
polyoxythylated castor oil. When used in
combination with doxorubicin, Paclitaxel
appears to enhance cardio toxicity by altering
doxorubicin pharmacokinetics and increasing
the myocyte formation of doxorubicinol, the
major metabolite of doxorubicin

SIGNS AND SYMPTOMS

Severe hypersensitivity reactions,
including death, reported.
Hypotension, bradycardia, ECG
abnormalities, conduction
abnormalities may occur. Fatal
myocardial infarction 15 h into
infusion reported.

Signs and symptoms

sinus bradycardia
Heart block
Premature ventricular contraction
Ventricular tachycardia
severe hypotension
bone marrow suppression
peripheral neurotoxicity and
mucositis.

ANTIDOTE
There is no known antidote. There is
no specific antidote for overdose.
Supportive therapy will help sustain
the patients in toxicity. Resuscitate if
indicated